title: Ultrasound‑targeted microbubble destruction enhances gene transduction of adeno-associated virus in a less-permissive cell type, NIH/3T3.
abstract: Adeno‑associated virus (AAV) is a common vector utilized in gene therapy. The NIH/3T3 cell line, which is a potential induced pluripotent stem (iPS) cell type, was identified to be a less-permissive cell type to AAV due to its defective endosomal processing. Ultrasound‑targeted microbubble destruction (UTMD) enhanced the gene transduction of AAV in permissive cells. However, there are no data concerning UTMD enhancement in less-permissive cells, and the exact mechanism of UTMD enhancement in cellular uptake is unclear. Greater knowledge concerning the rate-limiting steps in NIH/3T3 cells would aid in the elucidation of the mechanism of UTMD enhancement in the gene transduction of AAV. In the present study, UTMD enhanced the gene transduction of AAV in NIH/3T3 cells, suggesting that UTMD‑enhanced AAV‑mediated gene transduction may be beneficial for gene therapy in iPS cells. The dose dependence of UTMD enhancement indicated that mechanisms other than sonoporation were involved in the cellular uptake of AAV. However, UTMD did not greatly increase the gene transduction of AAV in NIH/3T3 cells. Additionally, the similar degree of enhancement in the two cell types resulted in no correlation between UTMD and endosomal processing. Future studies on UTMD‑mediated AAV transduction in other non- or less‑permissive cell types may aid in elucidating the exact mechanism of UTMD enhancement in cellular uptake.
authors.affiliation: Department of Ultrasound, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Jin
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Huiping
authors.initials: H
authors.lastname: Wang
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.forename: Lianfang
authors.initials: L
authors.lastname: Du
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D000229:Dependovirus / Q000502:physiology*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D045423:Microbubbles; D041681:NIH 3T3 Cells; D013016:Sound; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D019076:Transgenes; D056189:Viral Tropism